Quercetin is one of the most abundant dietary flavonoid compounds, and its mechanism for combating age-related neurodegenerative diseases is unclear. In this study, quercetin (35 and 70 mg kg⁻¹, orally administered for 4 weeks) was administered to 7-month-old aging mice (senescence-accelerated mouse prone 8 mice). As a result, it was found that quercetin could improve spatial learning and memory impairment displayed by aging mice in the Morris water maze. The results of immunoblotting reflected the protein expressions of the longevity factor (sirtuin1), inflammasomes (NLRP3 and ASC), synaptic marker (PSD95) and neurotrophic factors (BDNF and NGF) in the hippocampus of the brain. It indicated that the intervention of quercetin could increase the expression of sirtuin1 and prevent neuroinflammation, which was evident from the decrease in the protein levels of the astrocyte marker (GFAP) and inflammatory factors (cleaved-caspase 1, IL-1β and IL-18). In addition, quercetin could reduce the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in the hippocampus of aging mice. Current data indicated that quercetin might improve neuroinflammation in aging mice by regulating the Sirtuin1/NLRP3 pathway.

Vascular dementia (VaD), the second cause of dementia, is caused by chronic cerebral hypoperfusion, producing progressive damage to cerebral cortex, hippocampus, and white matter. Ligustilide (LIG), one of the main active ingredients of Angelica sinensis, exerts the neuroprotective effect on neurodegenerative diseases. However, the mechanism remains unclear. An in vivo model of bilateral common carotid artery occlusion and in vitro model of oxygen glucose deprivation (OGD) were employed in this study. LIG (20 or 40 mg/kg/day) was intragastrically administered to the VaD rats for four weeks. The results of the Morris water maze test demonstrated that LIG effectively ameliorated learning and memory deficiency in VaD rats. LIG obviously relieved neuronal oxidative stress damage by increasing the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH‐PX) and decreasing the level of malondialdehyde (MDA) in VaD rats. Nissl staining showed that LIG increased the number of the Nissl body in VaD rats. After LIG administration, the apoptotic‐related protein, Bax, was decreased and Bcl‐2 was increased in the hippocampus of VaD rats. Moreover, the expressions of sirtuin 1 (SIRT1) and protein disulfide isomerase (PDI) were decreased, binding immunoglobulin protein (BIP) and phospho‐inositol‐requiring enzyme‐1α (P‐IRE1α), X‐box binding protein 1 (XBP1s), and C/EBP‐homologous protein (CHOP) were increased in VaD rats. After LIG treatment, these changes were reversed. The immunofluorescence results further showed that LIG upregulated the expression of SIRT1 and downregulated the expression of P‐IRE1α in VaD rats. In addition, in vitro experiment showed that EX‐527 (SIRT1 inhibitor) partly abolished the inhibitory effect of LIG on the IRE1α/XBP1s/CHOP pathway. In conclusion, these studies indicated that LIG could improve cognitive impairment by regulating the SIRT1/IRE1α/XBP1s/CHOP pathway in VaD rats.

The flower of Hibiscus syriacus Linn is a well-known traditional Chinese medicine (TCM) and health food in China, which has been used to treat dysentery, vaginal discharge, and hemorrhoids. In this study, five polyphenols (compounds 1-5) and five fatty acids (compounds 6-10) were isolated from the ethanol extract of the flower of H. syriacus. The isolated compounds were characterized by spectroscopic techniques. Polyphenols, an important type of natural product, have variety of biological activities. Here, we employed LPS or H₂O₂-treated SH-SY5Y cell models to test the neuroprotective effect of compounds 1-10. Results found compounds 1-5 (concentration range was around 20 μM on LPS model, concentration range was around 13 μM on H₂O₂ model), not compounds 6-10, exhibited neuroprotective effect in LPS or H₂O₂-treated SH-SY5Y cell. PCR analysis showed that compounds 1-5 can effectively improve the mRNA expression of synapse-related gene and neurotrophic factors (Syp, NGF and BDNF) in LPS-treated SH-SY5Y cell. In addition, compounds 1-5 decreased the levels of ROS and MDA and increased the activities of SOD, GSH-Px and CAT in LPS-treated SH-SY5Y cell. Furthermore, compounds 1-5 inhibited neuroinflammation (TNF-α, IL-1β and IL-6) in LPS-treated SH-SY5Y cell. In conclusion, the polyphenols in the flower of H. syriacus could be a promising candidate for preventive effect of neuroinflammation.